This is a Cutting-Edge Basic Research Award R21 application designed to understand the mechanisms underlying the effects of drug addiction on cognitive performance. Exposure to abused drugs, such as opioids, degrades cognitive performance on many laboratory- based working memory tasks, such as the delayed non-match to sample (DNTMS) procedure. We hypothesize that drug-induced deficits in cognitive tasks may not necessarily reflect deficits in cognitive ability, but rather may result from a drug-induce decrease in the ability of non-drug vs. drug stimuli to reinforce behavior in these procedures. Aim #1 will assess the effects of reinforcer type (food vs. Remifentanil) and magnitude on work memory performance in non-dependent subjects. Aim #2 will assess the effects of opioid dependence and withdrawal on working memory performance maintained by food and remifentanil. Confirmation of our working hypothesis would challenge current thinking on the impact of drug addiction on addiction-related cognitive deficits, implicate reinforcer-specific neural circuits in addiction-related cognitive deficits, and provide an empirical foundation for th development of reinforcer-specific treatment strategies of these cognitive deficits.